Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGG814L)

• DOT Name: AFG2-interacting ribosome maturation factor (AIRIM)
• Synonyms: Ribosome biogenesis protein C1orf109
• Gene Name: AIRIM
• UniProt ID: AIRIM_HUMAN
• Pfam ID: PF15011
• Sequence:
  MTQDRPLLAVQEALKKCFPVVEEQQGLWQSALRDCQPLLSSLSNLAEQLQAAQNLRFEDV
  PALRAFPDLKERLRRKQLVAGDIVLDKLGERLAILLKVRDMVSSHVERVFQIYEQHADTV
  GIDAVLQPSAVSPSVADMLEWLQDIERHYRKSYLKRKYLLSSIQWGDLANIQALPKAWDR
  ISKDEHQDLVQDILLNVSFFLEE
• Function: Involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles. Acts together with AFG2A, AFG2B and CINP.

Molecular Interaction Atlas (MIA) of This DOT

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of AFG2-interacting ribosome maturation factor (AIRIM).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of AFG2-interacting ribosome maturation factor (AIRIM).	[7]

6 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of AFG2-interacting ribosome maturation factor (AIRIM).	[2]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of AFG2-interacting ribosome maturation factor (AIRIM).	[3]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of AFG2-interacting ribosome maturation factor (AIRIM).	[4]
Marinol	DM70IK5	Approved	Marinol decreases the expression of AFG2-interacting ribosome maturation factor (AIRIM).	[5]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of AFG2-interacting ribosome maturation factor (AIRIM).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of AFG2-interacting ribosome maturation factor (AIRIM).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [3] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [4] Oxidative stress modulates theophylline effects on steroid responsiveness. Biochem Biophys Res Commun. 2008 Dec 19;377(3):797-802.
• [5] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [6] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [7] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [8] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.